The main purpose of the proposed research project is to gain information on the immunobiology of human anaphylatoxins. The application of new methodology designed during the current year for the generation and isolation of C5a AT will substantially increase the yields of the isolated protein. This will make possible immunochemical and biological studies such as the correlation between C5a structure and function and the capacity of human C5a AT to elicit ultrastructural lesions in human skin. The mechanism by which C5a AT induces histamine release will be investigated by the elucidation of the nature of the cell receptor and the analysis of intracellular events set in motion by the AT action. The significance of the anaphylatoxin inactivator, a circulating carboxypeptidase B-like enzyme, will be investigated. Changes in AI levels during massive complement activation and/or anaphylactic shock will permit us to establish its physiopathological significance. Furthermore, since AI and/or its isoenzyme is also an inhibitor or bradikinin and a modulator of other peptide hormone systems in vivo, evaluation of its function could be a useful clinical diagnostic and therapeutic tool in diseases in which these systems participate.